@Electronic{igemHD2015,
  title                    = {iGEM Heidelberg 2015 Official Wiki},
  author                   = {iGEM Team Heidelberg},
  howpublished             = {http://2015.igem.org/Team:Heidelberg},
}

@article{Bagby2009,
   author = {Bagby, S. C. and Bergman, N. H. and Shechner, D. M. and Yen, C. and Bartel, D. P.},
   title = {A class I ligase ribozyme with reduced Mg2+ dependence: Selection, sequence analysis, and identification of functional tertiary interactions},
   journal = {RNA},
   volume = {15},
   number = {12},
   pages = {2129-46},
   note = {Bagby, Sarah C
Bergman, Nicholas H
Shechner, David M
Yen, Catherine
Bartel, David P
eng
GM61835/GM/NIGMS NIH HHS/
R01 GM061835/GM/NIGMS NIH HHS/
Howard Hughes Medical Institute/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
New York, N.Y.
2009/12/01 06:00
RNA. 2009 Dec;15(12):2129-46. doi: 10.1261/rna.1912509.},
   abstract = {The class I ligase was among the first ribozymes to have been isolated from random sequences and represents the catalytic core of several RNA-directed RNA polymerase ribozymes. The ligase is also notable for its catalytic efficiency and structural complexity. Here, we report an improved version of this ribozyme, arising from selection that targeted the kinetics of the chemical step. Compared with the parent ribozyme, the improved ligase achieves a modest increase in rate enhancement under the selective conditions and shows a sharp reduction in [Mg(2+)] dependence. Analysis of the sequences and kinetics of successful clones suggests which mutations play the greatest part in these improvements. Moreover, backbone and nucleobase interference maps of the parent and improved ligase ribozymes complement the newly solved crystal structure of the improved ligase to identify the functionally significant interactions underlying the catalytic ability and structural complexity of the ligase ribozyme.},
   keywords = {Base Sequence
Binding Sites
Crystallography, X-Ray
Genetic Variation
Kinetics
Ligases/*chemistry/genetics/*metabolism
Magnesium/*chemistry/*metabolism
Models, Molecular
Nucleic Acid Conformation
*Protein Interaction Domains and Motifs
RNA, Catalytic/*chemistry/genetics/*metabolism
Sequence Analysis, DNA},
   ISSN = {1469-9001 (Electronic)
1355-8382 (Linking)},
   DOI = {10.1261/rna.1912509},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19946040},
   year = {2009},
   type = {Journal Article}
}

@article{Balke2014,
   author = {Balke, D. and Zieten, I. and Strahl, A. and Muller, O. and Muller, S.},
   title = {Design and characterization of a twin ribozyme for potential repair of a deletion mutation within the oncogenic CTNNB1-DeltaS45 mRNA},
   journal = {ChemMedChem},
   volume = {9},
   number = {9},
   pages = {2128-37},
   note = {Balke, Darko
Zieten, Irene
Strahl, Anne
Muller, Oliver
Muller, Sabine
eng
Research Support, Non-U.S. Gov't
Germany
2014/08/13 06:00
ChemMedChem. 2014 Sep;9(9):2128-37. doi: 10.1002/cmdc.201402166. Epub 2014 Aug 11.},
   abstract = {RNA repair is an emerging strategy for gene therapy. Conventional gene therapy typically relies on the addition of the corrected DNA sequence of a defective gene to restore gene function. As an additional option, RNA repair allows alteration of the sequence of endogenous messenger RNAs (mRNAs). mRNA sequence alteration is either facilitated by intracellular spliceosome machinery or by the intrinsic catalytic activity of trans-acting ribozymes. Previously we developed twin ribozymes, derived from the hairpin ribozyme, by tandem duplication and demonstrated their potential for patchwise RNA repair. Herein we describe the development of such a twin ribozyme for potential repair of a deletion mutation in the oncogenic CTNNB1-DeltaS45 mRNA. We demonstrate that hairpin ribozyme units within the twin ribozyme can be adapted to efficiently cleave/ligate non-consensus substrates by introduction of compensatory mutations in the ribozyme. Thus, we show the twin ribozyme mediated repair of truncated CTNNB1 transcripts (up to 1000 nt length). Repair of the entire CTNNB1-DeltaS45 mRNA, although apparently possible in general, is hampered in vitro by the secondary structure of the transcript.},
   keywords = {Base Sequence
DNA Repair/*drug effects
Drug Design
*Gene Deletion
Kinetics
Molecular Sequence Data
Mutation/*drug effects
RNA Cleavage/drug effects
RNA, Catalytic/*chemical synthesis/*pharmacology
RNA, Messenger/*drug effects
beta Catenin/*drug effects/genetics},
   ISSN = {1860-7187 (Electronic)
1860-7179 (Linking)},
   DOI = {10.1002/cmdc.201402166},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/25112518},
   year = {2014},
   type = {Journal Article}
}

@article{Bartel1993,
   author = {Bartel, D. P. and Szostak, J. W.},
   title = {Isolation of new ribozymes from a large pool of random sequences [see comment]},
   journal = {Science},
   volume = {261},
   number = {5127},
   pages = {1411-8},
   note = {Bartel, D P
Szostak, J W
eng
Comment
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
1993/09/10
Science. 1993 Sep 10;261(5127):1411-8.},
   abstract = {An iterative in vitro selection procedure was used to isolate a new class of catalytic RNAs (ribozymes) from a large pool of random-sequence RNA molecules. These ribozymes ligate two RNA molecules that are aligned on a template by catalyzing the attack of a 3'-hydroxyl on an adjacent 5'-triphosphate--a reaction similar to that employed by the familiar protein enzymes that synthesize RNA. The corresponding uncatalyzed reaction also yields a 3',5'-phosphodiester bond. In vitro evolution of the population of new ribozymes led to improvement of the average ligation activity and the emergence of ribozymes with reaction rates 7 million times faster than the uncatalyzed reaction rate.},
   keywords = {Base Sequence
Biological Evolution
Catalysis
Kinetics
Magnesium/metabolism
Molecular Sequence Data
Mutation
Oligoribonucleotides/metabolism
RNA/*metabolism
RNA Ligase (ATP)/chemistry/isolation & purification/metabolism
RNA, Catalytic/chemistry/*isolation & purification/metabolism
Temperature
Templates, Genetic
NASA Discipline Exobiology
Non-NASA Center},
   ISSN = {0036-8075 (Print)
0036-8075 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7690155},
   year = {1993},
   type = {Journal Article}
}

@misc{Bartnicki2014,
   author = {BARTNICKI, F. and Kowalska, E. and PELS, K. and STRZAŁKA, W.},
   title = {Dna aptamers binding the histidine tag and their application},
   publisher = {Google Patents},
   url = {https://www.google.com/patents/WO2014185802A1?cl=en},
   year = {2014},
   type = {Generic}
}

@article{Beaudry1992,
   author = {Beaudry, A. A. and Joyce, G. F.},
   title = {Directed evolution of an RNA enzyme},
   journal = {Science},
   volume = {257},
   number = {5070},
   pages = {635-41},
   note = {Beaudry, A A
Joyce, G F
eng
AI30882/AI/NIAID NIH HHS/
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
1992/07/31
Science. 1992 Jul 31;257(5070):635-41.},
   abstract = {An in vitro evolution procedure was used to obtain RNA enzymes with a particular catalytic function. A population of 10(13) variants of the Tetrahymena ribozyme, a group I ribozyme that catalyzes sequence-specific cleavage of RNA via a phosphoester transfer mechanism, was generated. This enzyme has a limited ability to cleave DNA under conditions of high temperature or high MgCl2 concentration, or both. A selection constraint was imposed on the population of ribozyme variants such that only those individuals that carried out DNA cleavage under physiologic conditions were amplified to produce "progeny" ribozymes. Mutations were introduced during amplification to maintain heterogeneity in the population. This process was repeated for ten successive generations, resulting in enhanced (100 times) DNA cleavage activity.},
   keywords = {Animals
Base Composition
Base Sequence
Catalysis
DNA, Single-Stranded/metabolism
Genotype
Hot Temperature
Magnesium Chloride/pharmacology
Molecular Sequence Data
Mutagenesis
Mutagenesis, Site-Directed
Phenotype
Polymerase Chain Reaction
RNA, Catalytic/genetics/*metabolism
Substrate Specificity
Tetrahymena thermophila/*genetics
NASA Discipline Exobiology
Non-NASA Center},
   ISSN = {0036-8075 (Print)
0036-8075 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1496376},
   year = {1992},
   type = {Journal Article}
}

@article{Bock1992,
   author = {Bock, L. C. and Griffin, L. C. and Latham, J. A. and Vermaas, E. H. and Toole, J. J.},
   title = {Selection of single-stranded DNA molecules that bind and inhibit human thrombin},
   journal = {Nature},
   volume = {355},
   number = {6360},
   pages = {564-6},
   note = {Bock, L C
Griffin, L C
Latham, J A
Vermaas, E H
Toole, J J
eng
ENGLAND
1992/02/06
Nature. 1992 Feb 6;355(6360):564-6.},
   abstract = {Aptamers are double-stranded DNA or single-stranded RNA molecules that bind specific molecular targets. Large randomly generated populations can be enriched in aptamers by in vitro selection and polymerase chain reaction. But so far single-stranded DNA has not been investigated for aptamer properties, nor has a target protein been considered that does not interact physiologically with nucleic acid. Here we describe the isolation of single-stranded DNA aptamers to the protease thrombin of the blood coagulation cascade and report binding affinities in the range 25-200 nM. Sequence data from 32 thrombin aptamers, selected from a pool of DNA containing 60 nucleotides of random sequence, displayed a highly conserved 14-17-base region. Several of these aptamers at nanomolar concentrations inhibited thrombin-catalysed fibrin-clot formation in vitro using either purified fibrinogen or human plasma.},
   keywords = {Base Sequence
Blood Coagulation/drug effects
Cloning, Molecular
DNA, Single-Stranded/*isolation & purification
Dose-Response Relationship, Drug
Humans
In Vitro Techniques
Molecular Sequence Data
Polymerase Chain Reaction
Sequence Homology, Nucleic Acid
Thrombin/*antagonists & inhibitors
Thrombin Time},
   ISSN = {0028-0836 (Print)
0028-0836 (Linking)},
   DOI = {10.1038/355564a0},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1741036},
   year = {1992},
   type = {Journal Article}
}

@article{Breaker1994,
   author = {Breaker, R. R. and Joyce, G. F.},
   title = {A DNA enzyme that cleaves RNA},
   journal = {Chem Biol},
   volume = {1},
   number = {4},
   pages = {223-9},
   note = {Breaker, R R
Joyce, G F
eng
Research Support, U.S. Gov't, Non-P.H.S.
ENGLAND
1994/12/01 00:00
Chem Biol. 1994 Dec;1(4):223-9.},
   abstract = {BACKGROUND: Several types of RNA enzymes (ribozymes) have been identified in biological systems and generated in the laboratory. Considering the variety of known RNA enzymes and the similarity of DNA and RNA, it is reasonable to imagine that DNA might be able to function as an enzyme as well. No such DNA enzyme has been found in nature, however. We set out to identify a metal-dependent DNA enzyme using in vitro selection methodology. RESULTS: Beginning with a population of 10(14) DNAs containing 50 random nucleotides, we carried out five successive rounds of selective amplification, enriching for individuals that best promote the Pb(2+)-dependent cleavage of a target ribonucleoside 3'-O-P bond embedded within an otherwise all-DNA sequence. By the fifth round, the population as a whole carried out this reaction at a rate of 0.2 min-1. Based on the sequence of 20 individuals isolated from this population, we designed a simplified version of the catalytic domain that operates in an intermolecular context with a turnover rate of 1 min-1. This rate is about 10(5)-fold increased compared to the uncatalyzed reaction. CONCLUSIONS: Using in vitro selection techniques, we obtained a DNA enzyme that catalyzes the Pb(2+)-dependent cleavage of an RNA phosphoester in a reaction that proceeds with rapid turnover. The catalytic rate compares favorably to that of known RNA enzymes. We expect that other examples of DNA enzymes will soon be forthcoming.},
   keywords = {Catalysis
DNA/*metabolism
Kinetics
Lead/chemistry
RNA/*metabolism
RNA, Catalytic/*metabolism},
   ISSN = {1074-5521 (Print)
1074-5521 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9383394},
   year = {1994},
   type = {Journal Article}
}

@article{Buzayan1986,
   author = {Buzayan, J. M. and Gerlach, W. L. and Bruening, G.},
   title = {Nonenzymatic Cleavage and Ligation of Rnas Complementary to a Plant-Virus Satellite Rna},
   journal = {Nature},
   volume = {323},
   number = {6086},
   pages = {349-353},
   note = {E1371
Times Cited:285
Cited References Count:20},
   ISSN = {0028-0836},
   DOI = {DOI 10.1038/323349a0},
   url = {<Go to ISI>://WOS:A1986E137100051},
   year = {1986},
   type = {Journal Article}
}

@article{Cech1981,
   author = {Cech, T. R. and Zaug, A. J. and Grabowski, P. J.},
   title = {In vitro splicing of the ribosomal RNA precursor of Tetrahymena: involvement of a guanosine nucleotide in the excision of the intervening sequence},
   journal = {Cell},
   volume = {27},
   number = {3 Pt 2},
   pages = {487-96},
   note = {Cech, T R
Zaug, A J
Grabowski, P J
eng
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
1981/12/01
Cell. 1981 Dec;27(3 Pt 2):487-96.},
   abstract = {In previous studies of transcription and splicing of the ribosomal RNA precursor in isolated Tetrahymena nuclei, we found that the intervening sequence (IVS) was excised as a unique linear RNA molecule and was subsequently cyclized. In the present work, transcription at low monovalent cation concentration is found to inhibit splicing and to lead to the accumulation of a splicing intermediate. This intermediate contains splicing activity that either is tightly bound to the RNA or is part of the RNA molecule itself. The intermediate is able to complete the excision of the IVS when it is incubated with a monovalent cation (75 mM (NH4)2SO4), a divalent cation (5-10 mM MgCl2) and a guanosine compound (1 microM GTP, GDP, GMP or guanosine). ATP, UTP, CTP and guanosine compounds without 2' and 3' hydroxyl groups are inactive in causing excision of the IVS. Accurate excision of the IVS, cyclization of the IVS and (apparently) ligation of the 26S rRNA sequences bordering the IVS all take place under these conditions, suggesting that a single activity is responsible for all three reactions. During excision of the IVS, the 3' hydroxyl of the guanosine moiety becomes linked to the 5' end of the IVS RNA via a normal phosphodiester bond. When GTP is used to drive the reaction, it is added intact without hydrolysis. Based on these results, we propose that Tetrahymena pre-rRNA splicing occurs by a phosphoester transferase mechanism. According to this model, the guanosine cofactor provides the free 3' hydroxyl necessary to initiate a series of three transfers that results in splicing of the pre-rRNA and cyclization of the excised IVS.},
   keywords = {Animals
Base Sequence
Guanine Nucleotides/metabolism
Introns
Models, Biological
Molecular Sequence Data
Nucleic Acid Precursors/genetics/metabolism
*RNA Splicing
RNA, Ribosomal/genetics/metabolism
Tetrahymena thermophila/genetics/*metabolism},
   ISSN = {0092-8674 (Print)
0092-8674 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/6101203},
   year = {1981},
   type = {Journal Article}
}

@article{Crick1958,
   author = {Crick, F. H.},
   title = {On protein synthesis},
   journal = {Symp Soc Exp Biol},
   volume = {12},
   pages = {138-63},
   note = {CRICK, F H
eng
Not Available
1958/01/01
Symp Soc Exp Biol. 1958;12:138-63.},
   keywords = {Proteins/*metabolism
*PROTEINS/metabolism},
   ISSN = {0081-1386 (Print)
0081-1386 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/13580867},
   year = {1958},
   type = {Journal Article}
}

@article{Ellington1990,
   author = {Ellington, A. D. and Szostak, J. W.},
   title = {In vitro selection of RNA molecules that bind specific ligands},
   journal = {Nature},
   volume = {346},
   number = {6287},
   pages = {818-22},
   note = {Ellington, A D
Szostak, J W
eng
Research Support, Non-U.S. Gov't
ENGLAND
1990/08/30
Nature. 1990 Aug 30;346(6287):818-22.},
   abstract = {Subpopulations of RNA molecules that bind specifically to a variety of organic dyes have been isolated from a population of random sequence RNA molecules. Roughly one in 10(10) random sequence RNA molecules folds in such a way as to create a specific binding site for small ligands.},
   keywords = {Base Sequence
Binding Sites
Chromatography, Affinity
Cloning, Molecular
Coloring Agents/*metabolism
DNA/chemical synthesis
Ligands
Molecular Sequence Data
Molecular Structure
Nucleic Acid Conformation
Polymerase Chain Reaction
RNA/biosynthesis/*isolation & purification/metabolism
Templates, Genetic
Transcription, Genetic
Triazines/metabolism},
   ISSN = {0028-0836 (Print)
0028-0836 (Linking)},
   DOI = {10.1038/346818a0},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/1697402},
   year = {1990},
   type = {Journal Article}
}

@article{Forster1987,
   author = {Forster, A. C. and Symons, R. H.},
   title = {Self-Cleavage of Virusoid Rna Is Performed by the Proposed 55-Nucleotide Active-Site},
   journal = {Cell},
   volume = {50},
   number = {1},
   pages = {9-16},
   note = {J1550
Times Cited:236
Cited References Count:23},
   ISSN = {0092-8674},
   DOI = {Doi 10.1016/0092-8674(87)90657-X},
   url = {<Go to ISI>://WOS:A1987J155000004},
   year = {1987},
   type = {Journal Article}
}

@article{Grate1999,
   author = {Grate, D. and Wilson, C.},
   title = {Laser-mediated, site-specific inactivation of RNA transcripts},
   journal = {Proc Natl Acad Sci U S A},
   volume = {96},
   number = {11},
   pages = {6131-6},
   ISSN = {0027-8424 (Print)
0027-8424 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10339553},
   year = {1999},
   type = {Journal Article}
}

@article{Hershey1952,
   author = {Hershey, A. D. and Chase, M.},
   title = {Independent functions of viral protein and nucleic acid in growth of bacteriophage},
   journal = {J Gen Physiol},
   volume = {36},
   number = {1},
   pages = {39-56},
   year = {1952},
   type = {Journal Article}
}

@article{Himo2005,
   author = {Himo, F. and Lovell, T. and Hilgraf, R. and Rostovtsev, V. V. and Noodleman, L. and Sharpless, K. B. and Fokin, V. V.},
   title = {Copper(I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates},
   journal = {J Am Chem Soc},
   volume = {127},
   number = {1},
   pages = {210-6},
   note = {Himo, Fahmi
Lovell, Timothy
Hilgraf, Robert
Rostovtsev, Vsevolod V
Noodleman, Louis
Sharpless, K Barry
Fokin, Valery V
eng
GM28384/GM/NIGMS NIH HHS/
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
2005/01/06 09:00
J Am Chem Soc. 2005 Jan 12;127(1):210-6.},
   abstract = {Huisgen's 1,3-dipolar cycloadditions become nonconcerted when copper(I) acetylides react with azides and nitrile oxides, providing ready access to 1,4-disubstituted 1,2,3-triazoles and 3,4-disubstituted isoxazoles, respectively. The process is highly reliable and exhibits an unusually wide scope with respect to both components. Computational studies revealed a stepwise mechanism involving unprecedented metallacycle intermediates, which appear to be common for a variety of dipoles.},
   keywords = {Catalysis
Cations, Monovalent
Copper/*chemistry
Isoxazoles/*chemical synthesis
Models, Molecular
Nitriles/chemistry
Thermodynamics
Triazoles/*chemical synthesis},
   ISSN = {0002-7863 (Print)
0002-7863 (Linking)},
   DOI = {10.1021/ja0471525},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/15631470},
   year = {2005},
   type = {Journal Article}
}

@article{Jenison1994,
   author = {Jenison, R. D. and Gill, S. C. and Pardi, A. and Polisky, B.},
   title = {High-resolution molecular discrimination by RNA},
   journal = {Science},
   volume = {263},
   number = {5152},
   pages = {1425-9},
   note = {Jenison, R D
Gill, S C
Pardi, A
Polisky, B
eng
AI01051/AI/NIAID NIH HHS/
AI33098/AI/NIAID NIH HHS/
RR03283/RR/NCRR NIH HHS/
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
1994/03/11
Science. 1994 Mar 11;263(5152):1425-9.},
   abstract = {Species of RNA that bind with high affinity and specificity to the bronchodilator theophylline were identified by selection from an oligonucleotide library. One RNA molecule binds to theophylline with a dissociation constant Kd of 0.1 microM. This binding affinity is 10,000-fold greater than the RNA molecule's affinity for caffeine, which differs from theophylline only by a methyl group at nitrogen atom N-7. Analysis by nuclear magnetic resonance indicates that this RNA molecule undergoes a significant change in its conformation or dynamics upon theophylline binding. Binding studies of compounds chemically related to theophylline have revealed structural features required for the observed binding specificity. These results demonstrate the ability of RNA molecules to exhibit an extremely high degree of ligand recognition and discrimination.},
   keywords = {Base Sequence
Binding Sites
Binding, Competitive
DNA, Complementary/chemistry
Hydrogen Bonding
Magnetic Resonance Spectroscopy
Molecular Sequence Data
Molecular Structure
Nucleic Acid Conformation
RNA/chemistry/*metabolism
Sequence Analysis, DNA
Theophylline/chemistry/*metabolism
Xanthines/chemistry/metabolism},
   ISSN = {0036-8075 (Print)
0036-8075 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7510417},
   year = {1994},
   type = {Journal Article}
}

@article{Joyce1989,
   author = {Joyce, G. F.},
   title = {Amplification, mutation and selection of catalytic RNA},
   journal = {Gene},
   volume = {82},
   number = {1},
   pages = {83-7},
   note = {Joyce, G F
eng
NETHERLANDS
1989/10/15
Gene. 1989 Oct 15;82(1):83-7.},
   abstract = {RNA, by virtue of its genotypic and phenotypic properties, is a suitable substrate for molecular evolution in the laboratory. We have developed techniques for the rapid amplification, mutation and selection of catalytic RNA. By combining these techniques in an iterative fashion, we are attempting to construct an RNA-based evolving system. Such a system could be used to explore the catalytic potential of RNA.},
   keywords = {Biological Evolution
Catalysis
Gene Amplification
*Genetic Techniques
Mutation
Nucleic Acid Conformation
RNA, Catalytic
RNA, Ribosomal/*genetics
Selection, Genetic},
   ISSN = {0378-1119 (Print)
0378-1119 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2684778},
   year = {1989},
   type = {Journal Article}
}

@article{Kolb2001,
   author = {Kolb, H. C. and Finn, M. G. and Sharpless, K. B.},
   title = {Click Chemistry: Diverse Chemical Function from a Few Good Reactions},
   journal = {Angew Chem Int Ed Engl},
   volume = {40},
   number = {11},
   pages = {2004-2021},
   note = {Kolb, Hartmuth C.
Finn, M. G.
Sharpless, K. Barry
ENG
2001/07/04 10:00
Angew Chem Int Ed Engl. 2001 Jun 1;40(11):2004-2021.},
   abstract = {Examination of nature's favorite molecules reveals a striking preference for making carbon-heteroatom bonds over carbon-carbon bonds-surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon-heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C-C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C-X-C), an approach we call "click chemistry". Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect "spring-loaded" reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.},
   ISSN = {1521-3773 (Electronic)
1433-7851 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11433435},
   year = {2001},
   type = {Journal Article}
}

@article{Kruger1982,
   author = {Kruger, K. and Grabowski, P. J. and Zaug, A. J. and Sands, J. and Gottschling, D. E. and Cech, T. R.},
   title = {Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena},
   journal = {Cell},
   volume = {31},
   number = {1},
   pages = {147-57},
   note = {Kruger, K
Grabowski, P J
Zaug, A J
Sands, J
Gottschling, D E
Cech, T R
eng
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
1982/11/01
Cell. 1982 Nov;31(1):147-57.},
   abstract = {In the macronuclear rRNA genes of Tetrahymena thermophila, a 413 bp intervening sequence (IVS) interrupts the 26S rRNA-coding region. A restriction fragment of the rDNA containing the IVS and portions of the adjacent rRNA sequences (exons) was inserted downstream from the lac UV5 promoter in a recombinant plasmid. Transcription of this template by purified Escherichia coli RNA polymerase in vitro produced a shortened version of the pre-rRNA, which was then deproteinized. When incubated with monovalent and divalent cations and a guanosine factor, this RNA underwent splicing. The reactions that were characterized included the precise excision of the IVS, attachment of guanosine to the 5' end of the IVS, covalent cyclization of the IVS and ligation of the exons. We conclude that splicing activity is intrinsic to the structure of the RNA, and that enzymes, small nuclear RNAs and folding of the pre-rRNA into an RNP are unnecessary for these reactions. We propose that the IVS portion of the RNA has several enzyme-like properties that enable it to break and reform phosphodiester bonds. The finding of autocatalytic rearrangements of RNA molecules has implications for the mechanism and the evolution of other reactions that involve RNA.},
   keywords = {Animals
Base Sequence
DNA Restriction Enzymes
DNA Transposable Elements
*Genes
Lac Operon
Nucleic Acid Hybridization
Plasmids
RNA, Ribosomal/*genetics
Tetrahymena/*genetics
Transcription, Genetic},
   ISSN = {0092-8674 (Print)
0092-8674 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/6297745},
   year = {1982},
   type = {Journal Article}
}

@article{Lam2009,
   author = {Lam, B. J. and Joyce, G. F.},
   title = {Autocatalytic aptazymes enable ligand-dependent exponential amplification of RNA},
   journal = {Nat Biotechnol},
   volume = {27},
   number = {3},
   pages = {288-92},
   note = {Lam, Bianca J
Joyce, Gerald F
eng
5F32GM078691/GM/NIGMS NIH HHS/
F32 GM078691-03/GM/NIGMS NIH HHS/
R01 GM065130/GM/NIGMS NIH HHS/
R01 GM065130-07/GM/NIGMS NIH HHS/
R01GM065130/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
2009/02/24 09:00
Nat Biotechnol. 2009 Mar;27(3):288-92. doi: 10.1038/nbt.1528. Epub 2009 Feb 22.},
   abstract = {RNA enzymes have been developed that undergo self-sustained replication at a constant temperature in the absence of proteins. These RNA molecules amplify exponentially through a cross-replicative process, whereby two enzymes catalyze each other's synthesis by joining component oligonucleotides. Other RNA enzymes have been made to operate in a ligand-dependent manner by combining a catalytic domain with a ligand-binding domain (aptamer) to produce an 'aptazyme'. The principle of ligand-dependent RNA catalysis has now been extended to the cross-replicating RNA enzymes so that exponential amplification occurs in the presence, but not the absence, of the cognate ligand. The exponential growth rate of the RNA depends on the concentration of the ligand, allowing one to determine the concentration of ligand in a sample. This process is analogous to quantitative PCR (qPCR) but can be generalized to a wide variety of targets, including proteins and small molecules that are relevant to medical diagnostics and environmental monitoring.},
   keywords = {Aptamers, Nucleotide/*metabolism
Biocatalysis
Kinetics
Ligands
Nucleic Acid Conformation
Polynucleotide Ligases/*metabolism
RNA/*metabolism
RNA Ligase (ATP)/*metabolism
RNA, Catalytic/*metabolism},
   ISSN = {1546-1696 (Electronic)
1087-0156 (Linking)},
   DOI = {10.1038/nbt.1528},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19234448},
   year = {2009},
   type = {Journal Article}
}

@article{Levy2005,
   author = {Levy, M. and Griswold, K. E. and Ellington, A. D.},
   title = {Direct selection of trans-acting ligase ribozymes by in vitro compartmentalization},
   journal = {RNA},
   volume = {11},
   number = {10},
   pages = {1555-62},
   note = {Levy, Matthew
Griswold, Karl E
Ellington, Andrew D
eng
8R01 EB002043/EB/NIBIB NIH HHS/
Comparative Study
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
New York, N.Y.
2005/09/01 09:00
RNA. 2005 Oct;11(10):1555-62. Epub 2005 Aug 30.},
   abstract = {We have used a compartmentalized in vitro selection method to directly select for ligase ribozymes that are capable of acting on and turning over separable oligonucleotide substrates. Starting from a degenerate pool, we selected a trans-acting variant of the Bartel class I ligase which statistically may have been the only active variant in the starting pool. The isolation of this sequence from the population suggests that this selection method is extremely robust at selecting optimal ribozymes and should, therefore, prove useful for the selection and optimization of other trans-acting nucleic acid catalysts capable of multiple turnover catalysis.},
   keywords = {Base Pairing
Base Sequence
Cloning, Molecular
DNA/chemistry
Emulsions
Flow Cytometry
Fluorescein
Fluorescent Dyes
Genetic Variation
Hydrazines
In Vitro Techniques
Kinetics
Ligases/*metabolism
Microspheres
Models, Chemical
Nucleic Acid Amplification Techniques
Nucleic Acid Conformation
RNA, Catalytic/*chemistry/genetics/*isolation & purification/metabolism
Sequence Analysis, RNA
Substrate Specificity
Transcription, Genetic},
   ISSN = {1355-8382 (Print)
1355-8382 (Linking)},
   DOI = {10.1261/rna.2121705},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16131588},
   year = {2005},
   type = {Journal Article}
}

@article{Levy2005,
   author = {Levy, M. and Griswold, K. E. and Ellington, A. D.},
   title = {Direct selection of trans-acting ligase ribozymes by in vitro compartmentalization},
   journal = {RNA},
   volume = {11},
   number = {10},
   pages = {1555-62},
   note = {Levy, Matthew
Griswold, Karl E
Ellington, Andrew D
eng
8R01 EB002043/EB/NIBIB NIH HHS/
Comparative Study
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
New York, N.Y.
2005/09/01 09:00
RNA. 2005 Oct;11(10):1555-62. Epub 2005 Aug 30.},
   abstract = {We have used a compartmentalized in vitro selection method to directly select for ligase ribozymes that are capable of acting on and turning over separable oligonucleotide substrates. Starting from a degenerate pool, we selected a trans-acting variant of the Bartel class I ligase which statistically may have been the only active variant in the starting pool. The isolation of this sequence from the population suggests that this selection method is extremely robust at selecting optimal ribozymes and should, therefore, prove useful for the selection and optimization of other trans-acting nucleic acid catalysts capable of multiple turnover catalysis.},
   keywords = {Base Pairing
Base Sequence
Cloning, Molecular
DNA/chemistry
Emulsions
Flow Cytometry
Fluorescein
Fluorescent Dyes
Genetic Variation
Hydrazines
In Vitro Techniques
Kinetics
Ligases/*metabolism
Microspheres
Models, Chemical
Nucleic Acid Amplification Techniques
Nucleic Acid Conformation
RNA, Catalytic/*chemistry/genetics/*isolation & purification/metabolism
Sequence Analysis, RNA
Substrate Specificity
Transcription, Genetic},
   ISSN = {1355-8382 (Print)
1355-8382 (Linking)},
   DOI = {10.1261/rna.2121705},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16131588},
   year = {2005},
   type = {Journal Article}
}

@article{Lincoln2009,
   author = {Lincoln, T. A. and Joyce, G. F.},
   title = {Self-sustained replication of an RNA enzyme},
   journal = {Science},
   volume = {323},
   number = {5918},
   pages = {1229-32},
   note = {Lincoln, Tracey A
Joyce, Gerald F
eng
R01 GM065130/GM/NIGMS NIH HHS/
R01 GM065130-07/GM/NIGMS NIH HHS/
R01GM065130/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
2009/01/10 09:00
Science. 2009 Feb 27;323(5918):1229-32. doi: 10.1126/science.1167856. Epub 2009 Jan 8.},
   abstract = {An RNA enzyme that catalyzes the RNA-templated joining of RNA was converted to a format whereby two enzymes catalyze each other's synthesis from a total of four oligonucleotide substrates. These cross-replicating RNA enzymes undergo self-sustained exponential amplification in the absence of proteins or other biological materials. Amplification occurs with a doubling time of about 1 hour and can be continued indefinitely. Populations of various cross-replicating enzymes were constructed and allowed to compete for a common pool of substrates, during which recombinant replicators arose and grew to dominate the population. These replicating RNA enzymes can serve as an experimental model of a genetic system. Many such model systems could be constructed, allowing different selective outcomes to be related to the underlying properties of the genetic system.},
   keywords = {Base Pairing
Biocatalysis
Directed Molecular Evolution
Kinetics
Nucleic Acid Conformation
Oligonucleotides/*metabolism
Polynucleotide Ligases/*chemistry/metabolism
RNA, Catalytic/chemistry/*metabolism},
   ISSN = {1095-9203 (Electronic)
0036-8075 (Linking)},
   DOI = {10.1126/science.1167856},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19131595},
   year = {2009},
   type = {Journal Article}
}

@article{Lorenz2015,
   author = {Lorenz, D. A. and Song, J. M. and Garner, A. L.},
   title = {High-throughput platform assay technology for the discovery of pre-microrna-selective small molecule probes},
   journal = {Bioconjug Chem},
   volume = {26},
   number = {1},
   pages = {19-23},
   note = {Lorenz, Daniel A
Song, James M
Garner, Amanda L
eng
Research Support, Non-U.S. Gov't
2014/12/17 06:00
Bioconjug Chem. 2015 Jan 21;26(1):19-23. doi: 10.1021/bc500544v. Epub 2014 Dec 17.},
   abstract = {MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.},
   keywords = {Biocatalysis
Drug Discovery/*methods
High-Throughput Screening Assays/*methods
MicroRNAs/*metabolism
Molecular Probes/*chemistry/*metabolism
Ribonuclease III/metabolism
Substrate Specificity},
   ISSN = {1520-4812 (Electronic)
1043-1802 (Linking)},
   DOI = {10.1021/bc500544v},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/25506628},
   year = {2015},
   type = {Journal Article}
}

@article{Matsumura2009,
   author = {Matsumura, S. and Ohmori, R. and Saito, H. and Ikawa, Y. and Inoue, T.},
   title = {Coordinated control of a designed trans-acting ligase ribozyme by a loop-receptor interaction},
   journal = {FEBS Lett},
   volume = {583},
   number = {17},
   pages = {2819-26},
   note = {Matsumura, Shigeyoshi
Ohmori, Rei
Saito, Hirohide
Ikawa, Yoshiya
Inoue, Tan
eng
Research Support, Non-U.S. Gov't
Netherlands
2009/07/28 09:00
FEBS Lett. 2009 Sep 3;583(17):2819-26. doi: 10.1016/j.febslet.2009.07.036. Epub 2009 Jul 23.},
   abstract = {We previously developed a synthetic cis-acting RNA ligase ribozyme with 3'-5' joining activity termed "DSL" (designed and selected ligase). DSL was easily transformed into a trans-acting form because of its highly modular architecture. In this study, we investigated the modular properties and turnover capabilities of a trans-acting DSL, tDSL-1/GUAA. tDSL-1/GUAA exhibited remarkably high activity compared with the parental cis-acting DSL, and it attained a high turnover number. Taken together, the results indicate that a loop-receptor interaction plays a significant role in determining the activity of the trans-acting ribozyme and in its ability to perform multiple turnovers of the reaction.},
   keywords = {Base Pairing
Base Sequence
Molecular Sequence Data
*Nucleic Acid Conformation
RNA Ligase (ATP)/*chemistry/genetics/*metabolism
RNA, Catalytic/*chemistry/genetics/*metabolism
Substrate Specificity},
   ISSN = {1873-3468 (Electronic)
0014-5793 (Linking)},
   DOI = {10.1016/j.febslet.2009.07.036},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/19631647},
   year = {2009},
   type = {Journal Article}
}

@article{McKay2014,
   author = {McKay, C. S. and Finn, M. G.},
   title = {Click chemistry in complex mixtures: bioorthogonal bioconjugation},
   journal = {Chem Biol},
   volume = {21},
   number = {9},
   pages = {1075-101},
   note = {McKay, Craig S
Finn, M G
eng
R01 GM101421/GM/NIGMS NIH HHS/
Review
2014/09/23 06:00
Chem Biol. 2014 Sep 18;21(9):1075-101. doi: 10.1016/j.chembiol.2014.09.002.},
   abstract = {The selective chemical modification of biological molecules drives a good portion of modern drug development and fundamental biological research. While a few early examples of reactions that engage amine and thiol groups on proteins helped establish the value of such processes, the development of reactions that avoid most biological molecules so as to achieve selectivity in desired bond-forming events has revolutionized the field. We provide an update on recent developments in bioorthogonal chemistry that highlights key advances in reaction rates, biocompatibility, and applications. While not exhaustive, we hope this summary allows the reader to appreciate the rich continuing development of good chemistry that operates in the biological setting.},
   keywords = {Aldehydes/chemistry
Amines/chemistry
Amino Acids/chemistry
*Click Chemistry
Hydroxides/chemistry
Ketones/chemistry
Organometallic Compounds/chemistry
Prodrugs/chemistry/metabolism
Proteins/*chemistry/metabolism},
   ISSN = {1879-1301 (Electronic)
1074-5521 (Linking)},
   DOI = {10.1016/j.chembiol.2014.09.002},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/25237856},
   year = {2014},
   type = {Journal Article}
}

@article{Meyer2014,
   author = {Meyer, M. and Masquida, B.},
   title = {cis-Acting 5' hammerhead ribozyme optimization for in vitro transcription of highly structured RNAs},
   journal = {Methods Mol Biol},
   volume = {1086},
   pages = {21-40},
   note = {Meyer, Melanie
Masquida, Benoit
eng
Research Support, Non-U.S. Gov't
2013/10/19 06:00
Methods Mol Biol. 2014;1086:21-40. doi: 10.1007/978-1-62703-667-2_2.},
   abstract = {RNA-mediated biological processes usually require precise definition of 5' and 3' ends. RNA ends obtained by in vitro transcription using T7 RNA polymerase are often heterogeneous in length and sequence. An efficient strategy to overcome these drawbacks consists of inserting an RNA with known boundaries in between two ribozymes, usually a 5' hammerhead and a 3' hepatitis delta virus ribozymes, that cleave off the desired RNA. In practice, folding of the three RNAs challenges each other, potentially preventing thorough processing. Folding and cleavage of the 5' hammerhead ribozyme relies on a sequence of nucleotides belonging to the central RNA making it more sensitive than the usual 3' hepatitis delta virus ribozyme. The intrinsic stability of the central RNA may thus prevent correct processing of the full transcript. Here, we present a method in which incorporation of a full-length hammerhead ribozyme with a specific tertiary interaction prevents alternative folding with the lariat capping GIR1 ribozyme and enables complete cleavage in the course of the transcription. This strategy may be transposable for in vitro transcription of any highly structured RNA.},
   keywords = {Animals
Base Sequence
Blotting, Northern/methods
Cloning, Molecular/methods
Computer Simulation
Models, Molecular
Molecular Sequence Data
Nucleic Acid Conformation
RNA/chemistry/genetics/*metabolism
RNA, Catalytic/chemistry/genetics/*metabolism
RNA, Helminth/chemistry/genetics/*metabolism
Recombinant Fusion Proteins/chemistry/genetics/metabolism
Schistosoma/chemistry/*enzymology/genetics/metabolism
Software
Transcription, Genetic},
   ISSN = {1940-6029 (Electronic)
1064-3745 (Linking)},
   DOI = {10.1007/978-1-62703-667-2_2},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/24136596},
   year = {2014},
   type = {Journal Article}
}

@article{Ohmori2011,
   author = {Ohmori, R. and Saito, H. and Ikawa, Y. and Fujita, Y. and Inoue, T.},
   title = {Self-replication reactions dependent on tertiary interaction motifs in an RNA ligase ribozyme},
   journal = {J Mol Evol},
   volume = {73},
   number = {3-4},
   pages = {221-9},
   note = {Ohmori, Rei
Saito, Hirohide
Ikawa, Yoshiya
Fujita, Yoshihiko
Inoue, Tan
eng
Research Support, Non-U.S. Gov't
Germany
2011/11/15 06:00
J Mol Evol. 2011 Oct;73(3-4):221-9. doi: 10.1007/s00239-011-9471-2. Epub 2011 Nov 12.},
   abstract = {RNA can function both as an informational molecule and as a catalyst in living organisms. This duality is the premise of the RNA world hypothesis. However, one flaw in the hypothesis that RNA was the most essential molecule in primitive life is that no RNA self-replicating system has been found in nature. To verify whether RNA has the potential for self-replication, we constructed a new RNA self-assembling ribozyme that could have conducted an evolvable RNA self-replication reaction. The artificially designed, in vitro selected ligase ribozyme was employed as a prototype for a self-assembling ribozyme. The ribozyme is composed of two RNA fragments (form R1.Z1) that recognize another R1.Z1 molecule as their substrate and perform the high turnover ligation reaction via two RNA tertiary interaction motifs. Furthermore, the substrate recognition of R1.Z1 is tolerant of mutations, generating diversity in the corresponding RNA self-replicating network. Thus, we propose that our system implies the significance of RNA tertiary motifs in the early RNA molecular evolution of the RNA world.},
   keywords = {Base Pairing
Base Sequence
Binding Sites
Evolution, Molecular
Kinetics
Ligases/chemical synthesis/*chemistry
Models, Genetic
Models, Molecular
Molecular Sequence Data
*Nucleotide Motifs
RNA Folding
RNA, Catalytic/chemical synthesis/*chemistry},
   ISSN = {1432-1432 (Electronic)
0022-2844 (Linking)},
   DOI = {10.1007/s00239-011-9471-2},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22080218},
   year = {2011},
   type = {Journal Article}
}

@article{Paige2011,
   author = {Paige, J. S. and Wu, K. Y. and Jaffrey, S. R.},
   title = {RNA mimics of green fluorescent protein},
   journal = {Science},
   volume = {333},
   number = {6042},
   pages = {642-6},
   note = {Paige, Jeremy S
Wu, Karen Y
Jaffrey, Samie R
eng
NS064516/NS/NINDS NIH HHS/
R01 NS064516/NS/NINDS NIH HHS/
R01 NS064516-03/NS/NINDS NIH HHS/
T32 CA062948/CA/NCI NIH HHS/
T32 CA062948-14/CA/NCI NIH HHS/
T32CA062948/CA/NCI NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
2011/07/30 06:00
Science. 2011 Jul 29;333(6042):642-6. doi: 10.1126/science.1207339.},
   abstract = {Green fluorescent protein (GFP) and its derivatives have transformed the use and analysis of proteins for diverse applications. Like proteins, RNA has complex roles in cellular function and is increasingly used for various applications, but a comparable approach for fluorescently tagging RNA is lacking. Here, we describe the generation of RNA aptamers that bind fluorophores resembling the fluorophore in GFP. These RNA-fluorophore complexes create a palette that spans the visible spectrum. An RNA-fluorophore complex, termed Spinach, resembles enhanced GFP and emits a green fluorescence comparable in brightness with fluorescent proteins. Spinach is markedly resistant to photobleaching, and Spinach fusion RNAs can be imaged in living cells. These RNA mimics of GFP provide an approach for genetic encoding of fluorescent RNAs.},
   keywords = {Aptamers, Nucleotide/*chemistry/*metabolism
Benzyl Compounds/*chemistry/*metabolism
Biomimetics
Cell Nucleus/metabolism
Cytoplasmic Granules/metabolism
Cytosol/metabolism
*Fluorescence
Green Fluorescent Proteins/*chemistry
HEK293 Cells
Humans
Imidazolines/*chemistry/*metabolism
Molecular Mimicry
Nucleic Acid Conformation
Photobleaching
Protein Binding
RNA, Untranslated/metabolism
SELEX Aptamer Technique
Spectrometry, Fluorescence
Sucrose/pharmacology},
   ISSN = {1095-9203 (Electronic)
0036-8075 (Linking)},
   DOI = {10.1126/science.1207339},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21798953},
   year = {2011},
   type = {Journal Article}
}

@article{Prody1986,
   author = {Prody, G. A. and Bakos, J. T. and Buzayan, J. M. and Schneider, I. R. and Bruening, G.},
   title = {Autolytic processing of dimeric plant virus satellite RNA},
   journal = {Science},
   volume = {231},
   number = {4745},
   pages = {1577-80},
   note = {Prody, G A
Bakos, J T
Buzayan, J M
Schneider, I R
Bruening, G
eng
1986/03/28 00:00
Science. 1986 Mar 28;231(4745):1577-80.},
   abstract = {Associated with some plant viruses are small satellite RNA's that depend on the plant virus to provide protective coat protein and presumably at least some of the proteins necessary for satellite RNA replication. Multimeric forms of the satellite RNA of tobacco ringspot virus are probable in vivo precursors of the monomeric satellite RNA. Evidence is presented for the in vitro autolytic processing of dimeric and trimeric forms of this satellite RNA. The reaction generates biologically active monomeric satellite RNA, apparently is reversible to form dimeric RNA from monomeric RNA, and does not require an enzyme for its catalysis.},
   ISSN = {0036-8075 (Print)
0036-8075 (Linking)},
   DOI = {10.1126/science.231.4745.1577},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17833317},
   year = {1986},
   type = {Journal Article}
}

@article{Santoro1997,
   author = {Santoro, S. W. and Joyce, G. F.},
   title = {A general purpose RNA-cleaving DNA enzyme},
   journal = {Proc Natl Acad Sci U S A},
   volume = {94},
   number = {9},
   pages = {4262-6},
   note = {Santoro, S W
Joyce, G F
eng
Research Support, Non-U.S. Gov't
1997/04/29
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4262-6.},
   abstract = {An in vitro selection procedure was used to develop a DNA enzyme that can be made to cleave almost any targeted RNA substrate under simulated physiological conditions. The enzyme is comprised of a catalytic domain of 15 deoxynucleotides, flanked by two substrate-recognition domains of seven to eight deoxynucleotides each. The RNA substrate is bound through Watson-Crick base pairing and is cleaved at a particular phosphodiester located between an unpaired purine and a paired pyrimidine residue. Despite its small size, the DNA enzyme has a catalytic efficiency (kcat/Km) of approximately 10(9) M-1.min-1 under multiple turnover conditions, exceeding that of any other known nucleic acid enzyme. Its activity is dependent on the presence of Mg2+ ion. By changing the sequence of the substrate-recognition domains, the DNA enzyme can be made to target different RNA substrates. In this study, for example, it was directed to cleave synthetic RNAs corresponding to the start codon region of HIV-1 gag/pol, env, vpr, tat, and nef mRNAs.},
   keywords = {*DNA, Catalytic
DNA, Single-Stranded/*metabolism
Genes, Viral
*Hiv-1
Oligodeoxyribonucleotides/metabolism
Oligoribonucleotides/metabolism
RNA, Catalytic/metabolism
RNA, Messenger/*metabolism
RNA, Viral/*metabolism
Selection, Genetic},
   ISSN = {0027-8424 (Print)
0027-8424 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9113977},
   year = {1997},
   type = {Journal Article}
}

@article{Santoro1998,
   author = {Santoro, S. W. and Joyce, G. F.},
   title = {Mechanism and utility of an RNA-cleaving DNA enzyme},
   journal = {Biochemistry},
   volume = {37},
   number = {38},
   pages = {13330-42},
   note = {Santoro, S W
Joyce, G F
eng
AI30882/AI/NIAID NIH HHS/
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
1998/09/28
Biochemistry. 1998 Sep 22;37(38):13330-42.},
   abstract = {We previously reported the in vitro selection of a general-purpose RNA-cleaving DNA enzyme that exhibits a catalytic efficiency (kcat/KM) exceeding that of any other known nucleic acid enzyme [Santoro, S. W. and Joyce, G. F. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 4262-4266]. This enzyme contains approximately 30 deoxynucleotides and can cleave almost any RNA substrate under simulated physiological conditions, recognizing the substrate through two Watson-Crick binding domains. The kinetics of cleavage under conditions of varying pH, choice of divalent metal cofactor, and divalent metal concentration are consistent with a chemical mechanism involving metal-assisted deprotonation of a 2'-hydroxyl of the substrate, leading to substrate cleavage. Kinetic measurements reveal that the enzyme strongly prefers cleavage of the substrate over ligation of the two cleavage products and that the enzyme's catalytic efficiency is limited by the rate of substrate binding. The enzyme displays a high level of substrate specificity, discriminating against RNAs that contain a single base mismatch within either of the two substrate-recognition domains. With appropriate design of the substrate-recognition domains, the enzyme exhibits a potent combination of high substrate sequence specificity and selectivity, high catalytic efficiency, and rapid catalytic turnover.},
   keywords = {Base Composition
Catalysis
Cations, Divalent
DNA/*chemistry/metabolism
*DNA, Catalytic
DNA, Single-Stranded/*metabolism
Kinetics
Metals/chemistry/metabolism
Oligonucleotides/chemistry/metabolism
RNA, Catalytic/*chemistry/metabolism
Substrate Specificity},
   ISSN = {0006-2960 (Print)
0006-2960 (Linking)},
   DOI = {10.1021/bi9812221},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9748341},
   year = {1998},
   type = {Journal Article}
}

@article{Sassanfar1993,
   author = {Sassanfar, M. and Szostak, J. W.},
   title = {An RNA motif that binds ATP},
   journal = {Nature},
   volume = {364},
   number = {6437},
   pages = {550-3},
   note = {Sassanfar, M
Szostak, J W
eng
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
ENGLAND
1993/08/05
Nature. 1993 Aug 5;364(6437):550-3.},
   abstract = {RNAs that contain specific high-affinity binding sites for small molecule ligands immobilized on a solid support are present at a frequency of roughly one in 10(10)-10(11) in pools of random sequence RNA molecules. Here we describe a new in vitro selection procedure designed to ensure the isolation of RNAs that bind the ligand of interest in solution as well as on a solid support. We have used this method to isolate a remarkably small RNA motif that binds ATP, a substrate in numerous biological reactions and the universal biological high-energy intermediate. The selected ATP-binding RNAs contain a consensus sequence, embedded in a common secondary structure. The binding properties of ATP analogues and modified RNAs show that the binding interaction is characterized by a large number of close contacts between the ATP and RNA, and by a change in the conformation of the RNA.},
   keywords = {Adenosine Triphosphate/*metabolism
Base Sequence
Binding Sites
Chromatography
Consensus Sequence
Dna
Molecular Sequence Data
Nucleic Acid Conformation
RNA/chemistry/isolation & purification/*metabolism
NASA Discipline Exobiology
NASA Discipline Number 52-20
NASA Program Exobiology
Non-NASA Center},
   ISSN = {0028-0836 (Print)
0028-0836 (Linking)},
   DOI = {10.1038/364550a0},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7687750},
   year = {1993},
   type = {Journal Article}
}

@article{Schmidt2000,
   author = {Schmidt, C. and Welz, R. and Muller, S.},
   title = {RNA double cleavage by a hairpin-derived twin ribozyme},
   journal = {Nucleic Acids Res},
   volume = {28},
   number = {4},
   pages = {886-94},
   note = {Schmidt, C
Welz, R
Muller, S
eng
Research Support, Non-U.S. Gov't
ENGLAND
2000/01/29
Nucleic Acids Res. 2000 Feb 15;28(4):886-94.},
   abstract = {The hairpin ribozyme is a small catalytic RNA that catalyses reversible sequence-specific RNA hydrolysis in trans. It consists of two domains, which interact with each other by docking in an antiparallel fashion. There is a region between the two domains acting as a flexible hinge for interdomain interactions to occur. Hairpin ribozymes with reverse-joined domains have been constructed by dissecting the domains at the hinge and rejoining them in reverse order. We have used both the conventional and reverse-joined hairpin ribozymes for the design of a hairpin-derived twin ribozyme. We show that this twin ribozyme cleaves a suitable RNA substrate at two specific sites while maintaining the target specificity of the individual monoribozymes. For characterisation of the studied ribozymes we have evaluated a quantitative assay of sequence-specific ribozyme activity using fluorescently labelled RNA substrates in conjunction with an automated DNA sequencer. This assay was found to be applicable with hairpin and hairpin-derived ribozymes. The results demonstrate the potential of hairpin ribozymes for multi-target strategies of RNA cleavage and suggest the possibility for employing hairpin-derived twin ribozymes as powerful tools for RNA manipulation in vitro and in vivo.},
   keywords = {Base Sequence
Hydrolysis
Kinetics
Molecular Sequence Data
Nucleic Acid Conformation
RNA/chemistry/*metabolism
RNA, Catalytic/*metabolism},
   ISSN = {1362-4962 (Electronic)
0305-1048 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10648779},
   year = {2000},
   type = {Journal Article}
}

@article{Schneider2012,
   author = {Schneider, Gregory F. and Dekker, Cees},
   title = {DNA sequencing with nanopores},
   journal = {Nat Biotech},
   volume = {30},
   number = {4},
   pages = {326-328},
   ISSN = {1087-0156},
   DOI = {10.1038/nbt.2181},
   url = {http://dx.doi.org/10.1038/nbt.2181},
   year = {2012},
   type = {Journal Article}
}

@article{Seeling1999,
   author = {Seelig, B. and Jaschke, A.},
   title = {A small catalytic RNA motif with Diels-Alderase activity},
   journal = {Chem Biol},
   volume = {6},
   number = {3},
   pages = {167-76},
   note = {Seelig, B
Jaschke, A
eng
Research Support, Non-U.S. Gov't
ENGLAND
1999/03/13
Chem Biol. 1999 Mar;6(3):167-76.},
   abstract = {BACKGROUND: The 'RNA world' hypothesis requires that RNA be able to catalyze a wide variety of chemical reactions. In vitro selection from combinatorial RNA libraries has been used to identify several catalytic activities, most of which have resulted in a self-modification of RNA at one of its constituents. The formation of carbon-carbon bonds is considered an essential prerequisite for a complex metabolism based on RNA. RESULTS: We describe the selection and characterization of new ribozymes that catalyze carbon-carbon bond formation by Diels-Alder reaction of a biotinylated maleimide with an RNA-tethered anthracene. Secondary structure analysis identified a 49-nucleotide RNA motif that accelerates the reaction about 20,000-fold. The motif has only 11 conserved nucleotides that are present in most of the selected sequences. The ribozyme motif is remarkably adaptable with respect to cofactor and metal-ion requirements. The motif was also re-engineered to give a 38-mer RNA that can act as a 'true' catalyst on short external substrate oligonucleotide-anthracene conjugates. CONCLUSIONS: We have identified a small, highly abundant RNA motif that can solve the complex task of forming two carbon-carbon bonds between two reactants in trans, a catalytic capacity useful for creating prebiotically relevant molecules. This is the smallest and fastest RNA catalyst for carbon-carbon bond formation reported to date.},
   keywords = {Algorithms
Base Sequence
Biotin/metabolism
Carbon/metabolism
Cloning, Molecular
Gene Library
Genetic Engineering
Kinetics
Maleimides/metabolism
Molecular Sequence Data
Nucleic Acid Conformation
RNA, Catalytic/chemistry/genetics/*metabolism},
   ISSN = {1074-5521 (Print)
1074-5521 (Linking)},
   DOI = {10.1016/S1074-5521(99)89008-5},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10074465},
   year = {1999},
   type = {Journal Article}
}

@article{Servanov2007,
   author = {Serganov, A. and Patel, D. J.},
   title = {Ribozymes, riboswitches and beyond: regulation of gene expression without proteins},
   journal = {Nat Rev Genet},
   volume = {8},
   number = {10},
   pages = {776-90},
   note = {Serganov, Alexander
Patel, Dinshaw J
eng
GM073618/GM/NIGMS NIH HHS/
Comparative Study
Research Support, N.I.H., Extramural
Review
England
2007/09/12 09:00
Nat Rev Genet. 2007 Oct;8(10):776-90. Epub 2007 Sep 11.},
   abstract = {Although various functions of RNA are carried out in conjunction with proteins, some catalytic RNAs, or ribozymes, which contribute to a range of cellular processes, require little or no assistance from proteins. Furthermore, the discovery of metabolite-sensing riboswitches and other types of RNA sensors has revealed RNA-based mechanisms that cells use to regulate gene expression in response to internal and external changes. Structural studies have shown how these RNAs can carry out a range of functions. In addition, the contribution of ribozymes and riboswitches to gene expression is being revealed as far more widespread than was previously appreciated. These findings have implications for understanding how cellular functions might have evolved from RNA-based origins.},
   keywords = {Animals
Binding Sites
Catalysis
Catalytic Domain
Evolution, Molecular
*Gene Expression Regulation
Humans
Models, Molecular
Nucleic Acid Conformation
RNA/chemistry/metabolism
RNA, Catalytic/chemistry/*metabolism
*Regulatory Sequences, Ribonucleic Acid
Structure-Activity Relationship},
   ISSN = {1471-0064 (Electronic)
1471-0056 (Linking)},
   DOI = {10.1038/nrg2172},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/17846637},
   year = {2007},
   type = {Journal Article}
}

@article{Sharmeen1988,
   author = {Sharmeen, L. and Kuo, M. Y. and Dinter-Gottlieb, G. and Taylor, J.},
   title = {Antigenomic RNA of human hepatitis delta virus can undergo self-cleavage},
   journal = {J Virol},
   volume = {62},
   number = {8},
   pages = {2674-9},
   note = {Sharmeen, L
Kuo, M Y
Dinter-Gottlieb, G
Taylor, J
eng
CA-06927/CA/NCI NIH HHS/
CC-22651/CC/ODCDC CDC HHS/
RR-05539/RR/NCRR NIH HHS/
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
1988/08/01
J Virol. 1988 Aug;62(8):2674-9.},
   abstract = {The structure and replication of the single-stranded circular RNA genome of hepatitis delta virus (HDV) are unique relative to those of known animal viruses, and yet there are real similarities between HDV and certain infectious RNAs of plants. Therefore, since some of the latter RNAs have been shown to undergo in vitro site-specific cleavage and even ligation, we tested the hypothesis that similar events might also occur for HDV RNA. In partial confirmation of this hypothesis, we found that in vitro the RNA complementary to the HDV genome, the antigenomic RNA, could undergo a self-cleavage that was not only more than 90% efficient but also occurred only at a single location. This cleavage was found to produce junction fragments consistent with a 5'-hydroxyl and a cyclic 2',3'-monophosphate. Since the observed cleavage was both site-specific and occurred only once per genome length, we propose that the site may be relevant to the normal intracellular replication of the HDV genome. Because the site is located almost adjacent to the 3' end of the delta antigen-coding region, the only known functional open reading frame of HDV, we suggest that the cleavage may have a role not only in genome replication but also in RNA processing, helping to produce a functional mRNA for the translation of delta antigen.},
   keywords = {Antigens, Viral/genetics
Base Sequence
Genes, Viral
Hepatitis Delta Virus/*genetics/immunology
Molecular Sequence Data
Molecular Weight
RNA/*metabolism
*RNA Processing, Post-Transcriptional
RNA, Antisense
RNA, Viral/*metabolism},
   ISSN = {0022-538X (Print)
0022-538X (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2455816},
   year = {1988},
   type = {Journal Article}
}

@article{Silverman2005,
   author = {Silverman, S. K.},
   title = {In vitro selection, characterization, and application of deoxyribozymes that cleave RNA},
   journal = {Nucleic Acids Res},
   volume = {33},
   number = {19},
   pages = {6151-63},
   note = {Silverman, Scott K
eng
Historical Article
Research Support, Non-U.S. Gov't
Review
England
2005/11/16 09:00
Nucleic Acids Res. 2005 Nov 11;33(19):6151-63. Print 2005.},
   abstract = {Over the last decade, many catalytically active DNA molecules (deoxyribozymes; DNA enzymes) have been identified by in vitro selection from random-sequence DNA pools. This article focuses on deoxyribozymes that cleave RNA substrates. The first DNA enzyme was reported in 1994 and cleaves an RNA linkage. Since that time, many other RNA-cleaving deoxyribozymes have been identified. Most but not all of these deoxyribozymes require a divalent metal ion cofactor such as Mg2+ to catalyze attack by a specific RNA 2'-hydroxyl group on the adjacent phosphodiester linkage, forming a 2',3'-cyclic phosphate and a 5'-hydroxyl group. Several deoxyribozymes that cleave RNA have utility for in vitro RNA biochemistry. Some DNA enzymes have been applied in vivo to degrade mRNAs, and others have been engineered into sensors. The practical impact of RNA-cleaving deoxyribozymes should continue to increase as additional applications are developed.},
   keywords = {Biochemistry/history
Biosensing Techniques
Catalysis
DNA, Catalytic/*chemistry/*metabolism
History, 20th Century
RNA/chemistry/*metabolism
RNA, Messenger/metabolism},
   ISSN = {1362-4962 (Electronic)
0305-1048 (Linking)},
   DOI = {10.1093/nar/gki930},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/16286368},
   year = {2005},
   type = {Journal Article}
}

@article{Soukup1999,
   author = {Soukup, G. A. and Breaker, R. R.},
   title = {Nucleic acid molecular switches},
   journal = {Trends Biotechnol},
   volume = {17},
   number = {12},
   pages = {469-76},
   note = {Soukup, G A
Breaker, R R
eng
Review
ENGLAND
1999/11/11
Trends Biotechnol. 1999 Dec;17(12):469-76.},
   abstract = {Natural and artificial ribozymes can catalyse a diverse range of chemical reactions. Through recent efforts in enzyme engineering, it has become possible to tailor the activity of ribozymes to respond allosterically to specific effector compounds. These allosteric ribozymes function as effector-dependent molecular switches that could find application as novel genetic-control elements, biosensor components or precision switches for use in nanotechnology.},
   keywords = {Allosteric Regulation
Base Sequence
*Biosensing Techniques
DNA/*chemistry
Genetic Engineering/*methods/trends
Models, Genetic
Models, Molecular
Molecular Sequence Data
Nucleic Acid Conformation
Oligonucleotides, Antisense/chemistry/genetics
RNA/*chemistry
RNA, Catalytic/*chemistry},
   ISSN = {0167-7799 (Print)
0167-7799 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/10557159},
   year = {1999},
   type = {Journal Article}
}

@article{Sullenger1994,
   author = {Sullenger, B. A. and Cech, T. R.},
   title = {Ribozyme-mediated repair of defective mRNA by targeted, trans-splicing},
   journal = {Nature},
   volume = {371},
   number = {6498},
   pages = {619-22},
   note = {Sullenger, B A
Cech, T R
eng
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
ENGLAND
1994/10/13
Nature. 1994 Oct 13;371(6498):619-22.},
   abstract = {Ribozymes can be targeted to cleave specific RNAs, which has led to much interest in their potential as gene inhibitors. Such trans-cleaving ribozymes join a growing list of agents that stop the flow of genetic information. Here we describe a different application of ribozymes for which they may be uniquely suited. By targeted trans-splicing, a ribozyme can replace a defective portion of RNA with a functional sequence. The self-splicing intron from Tetrahymena thermophila was previously shown to mediate trans-splicing of oligonucleotides in vitro. As a model system for messenger RNA repair, this group I intron was re-engineered to regenerate the proper coding capacity of short, truncated lacZ transcripts. Trans-splicing was efficient in vitro and proceeded in Escherichia coli to generate translatable lacZ messages. Targeted trans-splicing represents a general means of altering the sequence of specified transcripts and may provide a new approach to the treatment of many genetic diseases.},
   keywords = {Animals
Base Sequence
DNA, Protozoan
Escherichia coli/genetics
Introns
Lac Operon
Molecular Sequence Data
*RNA Splicing
RNA, Catalytic/*metabolism
RNA, Messenger/*metabolism
RNA, Protozoan
Tetrahymena thermophila/genetics/metabolism},
   ISSN = {0028-0836 (Print)
0028-0836 (Linking)},
   DOI = {10.1038/371619a0},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/7935797},
   year = {1994},
   type = {Journal Article}
}

@article{Tang1997,
   author = {Tang, J. and Breaker, R. R.},
   title = {Rational design of allosteric ribozymes},
   journal = {Chem Biol},
   volume = {4},
   number = {6},
   pages = {453-9},
   note = {Tang, J
Breaker, R R
eng
Research Support, Non-U.S. Gov't
ENGLAND
1997/06/01
Chem Biol. 1997 Jun;4(6):453-9.},
   abstract = {BACKGROUND: Efficient operation of cellular processes relies on the strict control that each cell exerts over its metabolic pathways. Some protein enzymes are subject to allosteric regulation, in which binding sites located apart from the enzyme's active site can specifically recognize effector molecules and alter the catalytic rate of the enzyme via conformational changes. Although RNA also performs chemical reactions, no ribozymes are known to operate as true allosteric enzymes in biological systems. It has recently been established that small-molecule receptors can readily be made of RNA, as demonstrated by the in vitro selection of various RNA aptamers that can specifically bind corresponding ligand molecules. We set out to examine whether the catalytic activity of an existing ribozyme could be brought under the control of an effector molecule by designing conjoined aptamer-ribozyme complexes. RESULTS: By joining an ATP-binding RNA to a self-cleaving ribozyme, we have created the first example of an allosteric ribozyme that has a catalytic rate that can be controlled by ATP. A 180-fold reduction in rate is observed upon addition of either adenosine or ATP, but no inhibition is detected in the presence of dATP or other nucleoside triphosphates. Mutations in the aptamer domain that are expected to eliminate ATP binding or that increase the distance between aptamer and ribozyme domains result in a loss of ATP-specific allosteric control. Using a similar design approach, allosteric hammerhead ribozymes that are activated in the presence of ATP were created and another ribozyme that can be controlled by theophylline was created. CONCLUSIONS: The catalytic features of these conjoined aptamer-ribozyme constructs demonstrate that catalytic RNAs can also be subject to allosteric regulation-a key feature of certain protein enzymes. Moreover, by using simple rational design strategies, it is now possible to engineer new catalytic polynucleotides which have rates that can be tightly and specifically controlled by small effector molecules.},
   keywords = {Adenosine/pharmacology
Adenosine Triphosphate/metabolism/*pharmacology
Allosteric Regulation
Base Sequence
DNA Primers
Electrophoresis, Polyacrylamide Gel
Enzyme Inhibitors/pharmacology
*Genetic Engineering
Kinetics
Molecular Sequence Data
Mutation
Nucleotides/metabolism/pharmacology
Polymerase Chain Reaction
RNA/genetics/metabolism
RNA, Catalytic/chemistry/genetics/*metabolism
Theophylline/pharmacology},
   ISSN = {1074-5521 (Print)
1074-5521 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9224568},
   year = {1997},
   type = {Journal Article}
}

@article{Travascio1998,
   author = {Travascio, P. and Li, Y. and Sen, D.},
   title = {DNA-enhanced peroxidase activity of a DNA-aptamer-hemin complex},
   journal = {Chem Biol},
   volume = {5},
   number = {9},
   pages = {505-17},
   note = {Travascio, P
Li, Y
Sen, D
eng
Research Support, Non-U.S. Gov't
ENGLAND
1998/09/30
Chem Biol. 1998 Sep;5(9):505-17.},
   abstract = {BACKGROUND: In vitro selection (SELEX) previously identified short single-stranded DNAs that specifically bound N-methylmesoporphyrin IX (NMM), a stable transition-state analogue for porphyrin-metallation reactions. Interestingly, iron(III)-protoporphyrin (hemin) was a good competitive inhibitor for the DNA-catalyzed metallation reaction, and appeared to bind strongly to the NMM-binding DNA aptamers. We investigated the peroxidase activity of the aptamer-hemin complexes to see if the DNA component of the complex, like the apoenzymes in protein peroxidases, could enhance the low intrinsic peroxidatic activity of hemin. RESULTS: Two porphyrin-binding DNA aptamers bound hemin with submicromolar affinity. The aptamer-hemin complexes had significantly higher peroxidase activity than hemin alone, under physiological conditions. The Vobs of the PS2.M-hemin complex was 250 times greater than that of hemin alone, and significantly superior to a previously reported hemin-catalytic-antibody complex. Preliminary spectroscopic evidence suggests the coordination of the hemin iron in the complex changes, such that the complex more closely resembles horseradish peroxidase and other heme proteins rather than hemin. CONCLUSIONS: A new class of catalytic activity for nucleic acids is reported. The aptamer-hemin complexes described are novel DNA enzymes and their study will help elucidate the structural and functional requirements of peroxidase enzymes in general and the ways that a nucleic acid 'apoenzyme' might work to enhance the intrinsic peroxidatic ability of hemin. These aptamer-hemin complexes could be regarded as prototypes for redox-catalyzing ribozymes in a primordial 'RNA world'.},
   keywords = {Catalysis
DNA, Single-Stranded/*metabolism
Detergents
Hemin/*metabolism
Hydrogen-Ion Concentration
Macromolecular Substances
Mesoporphyrins/metabolism
Nucleic Acid Conformation
Octoxynol
Oligonucleotides/*metabolism
Peroxidases/*metabolism
Spectrophotometry, Atomic
Spectrophotometry, Ultraviolet},
   ISSN = {1074-5521 (Print)
1074-5521 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/9751647},
   year = {1998},
   type = {Journal Article}
}

@article{Tseng2011,
   author = {Tseng, C. Y. and Ashrafuzzaman, M. and Mane, J. Y. and Kapty, J. and Mercer, J. R. and Tuszynski, J. A.},
   title = {Entropic fragment-based approach to aptamer design},
   journal = {Chem Biol Drug Des},
   volume = {78},
   number = {1},
   pages = {1-13},
   note = {Tseng, Chih-Yuan
Ashrafuzzaman, Md
Mane, Jonathan Y
Kapty, Janice
Mercer, John R
Tuszynski, Jack A
eng
Research Support, Non-U.S. Gov't
England
2011/04/19 06:00
Chem Biol Drug Des. 2011 Jul;78(1):1-13. doi: 10.1111/j.1747-0285.2011.01125.x. Epub 2011 May 25.},
   abstract = {Aptamers are short RNA/DNA sequences that are identified through the process of systematic evolution of ligands by exponential enrichment and that bind to diverse biomolecular targets. Aptamers have strong and specific binding through molecular recognition and are promising tools in studying molecular biology. They are recognized as having potential therapeutic and diagnostic clinical applications. The success of the systematic evolution of ligands by exponential enrichment process requires that the RNA/DNA pools used in the process have a sufficient level of sequence diversity and structural complexity. While the systematic evolution of ligands by exponential enrichment technology is well developed, it remains a challenge in the efficient identification of correct aptamers. In this article, we propose a novel information-driven approach to a theoretical design of aptamer templates based solely on the knowledge regarding the biomolecular target structures. We have investigated both theoretically and experimentally the applicability of the proposed approach by considering two specific targets: the serum protein thrombin and the cell membrane phospholipid phosphatidylserine. Both of these case studies support our method and indicate a promising advancement in theoretical aptamer design. In unfavorable cases where the designed sequences show weak binding affinity, these template sequences can be still modified to enhance their affinities without going through the systematic evolution of ligands by exponential enrichment process.},
   keywords = {Aptamers, Nucleotide/*chemistry/pharmacology
*Drug Design
*Entropy
Molecular Dynamics Simulation
Phosphatidylserines/chemistry
Structure-Activity Relationship
Thrombin/chemistry},
   ISSN = {1747-0285 (Electronic)
1747-0277 (Linking)},
   DOI = {10.1111/j.1747-0285.2011.01125.x},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21496214},
   year = {2011},
   type = {Journal Article}
}

@article{Tuerk1990,
   author = {Tuerk, C. and Gold, L.},
   title = {Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase},
   journal = {Science},
   volume = {249},
   number = {4968},
   pages = {505-10},
   note = {Tuerk, C
Gold, L
eng
GM 19963/GM/NIGMS NIH HHS/
GM 28685/GM/NIGMS NIH HHS/
Research Support, U.S. Gov't, P.H.S.
1990/08/03
Science. 1990 Aug 3;249(4968):505-10.},
   abstract = {High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species. Multiple rounds exponentially enrich the population for the highest affinity species that can be clonally isolated and characterized. In particular one eight-base region of an RNA that interacts with the T4 DNA polymerase was chosen and randomized. Two different sequences were selected by this procedure from the calculated pool of 65,536 species. One is the wild-type sequence found in the bacteriophage mRNA; one is varied from wild type at four positions. The binding constants of these two RNA's to T4 DNA polymerase are equivalent. These protocols with minimal modification can yield high-affinity ligands for any protein that binds nucleic acids as part of its function; high-affinity ligands could conceivably be developed for any target molecule.},
   keywords = {Base Sequence
*Biological Evolution
DNA-Directed DNA Polymerase/*metabolism
Escherichia coli/*enzymology
*Genes, Viral
Genetic Techniques
Ligands
*Models, Genetic
Molecular Sequence Data
Nucleic Acid Conformation
Polymerase Chain Reaction
RNA, Messenger/genetics/*metabolism
RNA, Viral/genetics/*metabolism
T-Phages/*enzymology
Transcription, Genetic},
   ISSN = {0036-8075 (Print)
0036-8075 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/2200121},
   year = {1990},
   type = {Journal Article}
}

@article{Wang2002,
   author = {Wang, D. Y. and Lai, B. H. and Feldman, A. R. and Sen, D.},
   title = {A general approach for the use of oligonucleotide effectors to regulate the catalysis of RNA-cleaving ribozymes and DNAzymes},
   journal = {Nucleic Acids Res},
   volume = {30},
   number = {8},
   pages = {1735-42},
   note = {Wang, Dennis Y
Lai, Beatrice H Y
Feldman, Anat R
Sen, Dipankar
eng
Research Support, Non-U.S. Gov't
England
2002/04/09 10:00
Nucleic Acids Res. 2002 Apr 15;30(8):1735-42.},
   abstract = {A general approach is described for controlling the RNA-cleaving activity of nucleic acid enzymes (ribozymes and DNAzymes) via the use of oligonucleotide effectors (regulators). In contrast to the previously developed approaches of allosteric and facilitator-mediated regulation of such enzymes, this approach, called 'expansive' regulation, requires that the regulator bind simultaneously to both enzyme and substrate to form a branched three-way complex. Such three-way enzyme-substrate-regulator complexes are catalytically competent relative to the structurally unstable enzyme-substrate complexes. Using the 8-17 and bipartite DNAzymes and the hammerhead ribozyme as model systems, 20- to 30-fold rate enhancements were achieved in the presence of regulators of engineered variants of the above three enzymes, even under unoptimized conditions. Broadly, using this approach ribozyme and DNAzyme variants that are amenable to regulation by oligonucleotide effectors can be designed even in the absence of any knowledge of the folded structure of the relevant ribozyme or DNAzyme. Expansive regulation therefore represents a new and potentially useful technology for both the regulation of nucleic acid enzymes and the detection of specific RNA transcripts.},
   keywords = {Base Sequence
Catalysis
DNA/metabolism
DNA, Catalytic/chemistry/genetics/*metabolism
Genetic Engineering/*methods
Kinetics
Macromolecular Substances
Models, Genetic
Nucleic Acid Conformation
Oligonucleotides/*metabolism
RNA/metabolism
RNA, Catalytic/chemistry/genetics/*metabolism},
   ISSN = {1362-4962 (Electronic)
0305-1048 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/11937626},
   year = {2002},
   type = {Journal Article}
}

@article{Winz2006,
   author = {Winz, M. L. and Samanta, A. and Benzinger, D. and Jaschke, A.},
   title = {Site-specific terminal and internal labeling of RNA by poly(A) polymerase tailing and copper-catalyzed or copper-free strain-promoted click chemistry},
   journal = {Nucleic Acids Res},
   volume = {40},
   number = {10},
   pages = {e78},
   note = {Winz, Marie-Luise
Samanta, Ayan
Benzinger, Dirk
Jaschke, Andres
eng
Research Support, Non-U.S. Gov't
England
2012/02/22 06:00
Nucleic Acids Res. 2012 May;40(10):e78. doi: 10.1093/nar/gks062. Epub 2012 Feb 16.},
   abstract = {The modification of RNA with fluorophores, affinity tags and reactive moieties is of enormous utility for studying RNA localization, structure and dynamics as well as diverse biological phenomena involving RNA as an interacting partner. Here we report a labeling approach in which the RNA of interest--of either synthetic or biological origin--is modified at its 3'-end by a poly(A) polymerase with an azido-derivatized nucleotide. The azide is later on conjugated via copper-catalyzed or strain-promoted azide-alkyne click reaction. Under optimized conditions, a single modified nucleotide of choice (A, C, G, U) containing an azide at the 2'-position can be incorporated site-specifically. We have identified ligases that tolerate the presence of a 2'-azido group at the ligation site. This azide is subsequently reacted with a fluorophore alkyne. With this stepwise approach, we are able to achieve site-specific, internal backbone-labeling of de novo synthesized RNA molecules.},
   keywords = {Adenosine Triphosphate/analogs & derivatives/chemistry
Azides/chemistry
Carbohydrates/chemistry
Catalysis
Click Chemistry/*methods
Copper/*chemistry
Escherichia coli/genetics
Fluorescent Dyes
Nucleotides/chemistry/metabolism
Nucleotidyltransferases/metabolism
Polynucleotide Adenylyltransferase/*metabolism
RNA/*chemistry/metabolism
Yeasts/enzymology},
   ISSN = {1362-4962 (Electronic)
0305-1048 (Linking)},
   DOI = {10.1093/nar/gks062},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22344697},
   year = {2012},
   type = {Journal Article}
}

Copper/*chemistry
Escherichia coli/genetics
Fluorescent Dyes
Nucleotides/chemistry/metabolism
Nucleotidyltransferases/metabolism
Polynucleotide Adenylyltransferase/*metabolism
RNA/*chemistry/metabolism
Yeasts/enzymology},
   ISSN = {1362-4962 (Electronic)
0305-1048 (Linking)},
   DOI = {10.1093/nar/gks062},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22344697},
   year = {2012},
   type = {Journal Article}
}

